The 1994 international transatlantic two-way satellite time and frequency transfer experiment: Preliminary results

The international transatlantic time and frequency transfer experiment was designed by participating laboratories and has been implemented during 1994 to test the international communications path involving a large number of transmitting stations. This paper will present empirically determined clock and time scale differences, time and frequency domain instabilities, and a representative power spectral density analysis. The experiments by the method of co-location which will allow absolute calibration of the participating laboratories have been performed. Absolute time differences and accuracy levels of this experiment will be assessed in the near future

Informing epidemic (research) responses in a timely fashion by knowledge management - a Zika virus use case

The response of pathophysiological research to emerging epidemics often occurs after the epidemic and, as a consequence, has little to no impact on improving patient outcomes or on developing high-quality evidence to inform clinical management strategies during the epidemic. Rapid and informed guidance of epidemic (research) responses to severe infectious disease outbreaks requires quick compilation and integration of existing pathophysiological knowledge. As a case study we chose the Zika virus (ZIKV) outbreak that started in 2015 to develop a proof-of-concept knowledge repository. To extract data from available sources and build a computationally tractable and comprehensive molecular interaction map we applied generic knowledge management software for literature mining, expert knowledge curation, data integration, reporting and visualization. A multi-disciplinary team of experts, including clinicians, virologists, bioinformaticians and knowledge management specialists, followed a pre-defined workflow for rapid integration and evaluation of available evidence. While conventional approaches usually require months to comb through the existing literature, the initial ZIKV KnowledgeBase (ZIKA KB) was completed within a few weeks. Recently we updated the ZIKA KB with additional curated data from the large amount of literature published since 2016 and made it publicly available through a web interface together with a step-by-step guide to ensure reproducibility of the described use case. In addition, a detailed online user manual is provided to enable the ZIKV research community to generate hypotheses, share knowledge, identify knowledge gaps, and interactively explore and interpret data. A workflow for rapid response during outbreaks was generated, validated and refined and is also made available. The process described here can be used for timely structuring of pathophysiological knowledge for future threats. The resulting structured biological knowledge is a helpful tool for computational data analysis and generation of predictive models and opens new avenues for infectious disease research. ZIKV Knowledgebase is available at www.zikaknowledgebase.eu

The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response

TANK-binding kinase 1 (TBK1) is of central importance for the induction of type-I interferon (IFN) in response to pathogens. We identified the DEAD-box helicase DDX3X as an interaction partner of TBK1. TBK1 and DDX3X acted synergistically in their ability to stimulate the IFN promoter, whereas RNAi-mediated reduction of DDX3X expression led to an impairment of IFN production. Chromatin immunoprecipitation indicated that DDX3X is recruited to the IFN promoter upon infection with Listeria monocytogenes, suggesting a transcriptional mechanism of action. DDX3X was found to be a TBK1 substrate in vitro and in vivo. Phosphorylation-deficient mutants of DDX3X failed to synergize with TBK1 in their ability to stimulate the IFN promoter. Overall, our data imply that DDX3X is a critical effector of TBK1 that is necessary for type I IFN induction

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

A T cell controlled molecular pathway regulating the IgH locus: CD40-mediated activation of the IgH 3' enhancer

Immunoglobulin heavy chain (IgH) class switch recombination and regulation of IgH expression levels are processes suggested to be controlled by the IgH 3' enhancer. Here we demonstrate that CD40 or IgM receptor stimulation of primary B cells results in transactivation of this enhancer. 4-Hydroxy-3-nitrophenylacetyl (NIP)-BSA induction of a K46 B cell line expressing a chimeric NIP-specific CD40 single chain receptor results in a ligand receptor-dependent response of a 3' enhancer ETS/AP-1 minimal promoter construct. Gel retardation analysis and genomic footprinting experiments reveal that CD40 or IgM induction recruits NFAB (nuclear factors of activated B cells) to the ETS/AP-1 motif. While IgM signalling recruits c-Fos, JunB and Elf-1 (NFAB-I), only JunB and Elf-1 were observed following CD40 signalling (NFAB-II). CD40 signalling, however, induces a Fos family-related partner for JunB, which may account for the transcriptional activity observed by NFAB-II in K46 cells. We propose a model whereby CD40 and IgM receptor-mediated signalling converge in the process of 3' enhancer activation in B lymphocytes. Our data provide a putative molecular explanation as to why CD40L-deficient mice, and possibly patients with hyper-IgM syndrome, are unable to undergo T cell-dependent class switch recombination but respond properly upon lipopolysaccharide-induced switch recombination

The psychosocial development and increased fluency of users of the speecheasy device: a multiple unit case study

This dissertation study explored the efficacy of the SpeechEasy® device for individuals who are gainfully employed stutterers and who participated in workplace education learning activities. This study attempted to fill a gap in the literature regarding efficacy of the SpeechEasy® device. It employed a qualitative multiple unit case study method, which explored six individuals` use of the SpeechEasy® device using an auto-ethnographic narrative theoretical framework based on the methodological tradition of Smith and Sparkes` (2008) five identity perspectives. Findings indicate participants` satisfaction with the SpeechEasy® device in reducing their stuttering. This led to improved confidence and self-image. They also reported their willingness to assume visible roles within their organizations that required fluent speech including increased participation in workplace training. In addition, the participants reported increased opportunities for promotion and job placement. The results of this study indicate that morale and efficiency in the workplace increases in organizations where individuals who stutter begin using the SpeechEasy device. Likewise, these individuals, including the researcher, recognize the personal advantage in developing higher levels of psychosocial development through an improved self-image and increased self-confidence brought about from using this devise. Employers and Speech Pathologists need to be aware of the findings of this study to enable them to assist their employees and clients who stutter in constructing plans that will lead to the purchase and use of the Speech Easy device. (Published By University of Alabama Libraries